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Purpose: To investigate the relationship between the structural parameters of trabecular bone obtained from CBCT imaging and the primary stability of dental implants. Materials and Methods: Sixty patients underwent implant placement followed by primary stability evaluation via measurement of the insertion torque (IT) and the implant stability quotient (ISQ). Gray values (GV) and the fractal dimension (FD) were also measured using pretreatment CBCT images. Results: FD values showed a positive and significant relationship with ISQ and IT values (P = .017 and P = .004, respectively). Additionally, there was a positive and significant correlation between GV and IT (P = .004) as well as between GV and ISQ (P = .010). FD and GV showed a considerable difference between the maxillary and mandibular jaws and were higher in the mandible. Only FD was significantly different between men and women and was higher in men. In the two age groups (older and younger than 45 years), only GV was considerably higher in people older than 45 (P < .05). Conclusions: Both fractal dimension and gray values obtained from CBCT are efficient methods for predicting the primary stability of the implant due to their relationship with ISQ and IT values. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether a recently introduced implant placement micromotor that provides site-specific, operatorindependent cancellous bone density measurements can detect the presence of a cortical bone layer and measure its thickness and density. Materials and Methods: An in vitro experiment was performed on six double-layer polyurethane foam blocks mimicking the jawbone with different cortical thickness/cancellous density combinations. The densities were measured using the micromotor after either removing the cortical layer or leaving it intact, both with and without irrigation. Results: The results were compared by means of nonparametric statistical tests. Independent of irrigation, the micromotor detected the cortical layer when it was left intact and accurately estimated its thickness. The micromotor did not discriminate between blocks when they were considered separately, but it did when they were grouped into four or three classes. Conclusions: The present study suggests that the micromotor may represent a valid device to quantitatively assess bone quality and density. If the micromotor can quantitatively distinguish different cortical/cancellous bone combinations in humans, it may be a helpful tool for performing finely tuned, patient-tailored preparations of the implant seat, making tooth rehabilitation in challenging clinical conditions more predictable. [ABSTRACT FROM AUTHOR]

Objectives: Fractal analysis is a numerical method that indicates the structural patterns and complexity of the trabecular bone on radiographs. The aim of this cross-sectional study was to evaluate the trabecular bone structure in systemically healthy patients and diabetes mellitus patients with periodontitis using fractal analysis. Method and materials: The study included 125 mandibular first molars of nonsmoker patients. The subjects were divided into five subgroups: diabetes mellitus patients with mild-moderate periodontitis, diabetes mellitus patients with advanced periodontitis, systemically healthy individuals with mild-moderate periodontitis, systemically healthy individuals with advanced periodontitis, and systemically healthy individuals with gingivitis (control group). Clinical periodontal parameters (pocket depth, bleeding on probing, clinical attachment loss, and bone loss) were recorded. Two specific sites located in the mesial-distal regions (n = 250) of the mandibular first molars were identified using periapical radiographs captured with a parallel technique. Fractal analysis values were calculated using the box-counting method. One-way analysis of variance (ANOVA), and Pearson correlation analysis were used forstatistical evaluation. Results: The highest fractal analysis values were observed in systemically healthy with gingivitis patients (mesial fractal analysis: 1.86 ± 0.01; distal fractal analysis: 1.85 ±0.01). Patients with periodontitis (mesial fractal analysis: 1.78 ±0.02; distal fractal analysis: 1.79 ± 0.01) exhibited lower fractal analysis values compared to the control group. There was no significant difference in mesial and distal fractal analysis values between all periodontitis groups. No correlation was found between age, sex, clinical attachment loss, bone loss, and fractal analysis (P>.05). Conclusions: Although fractal analysis values were lower in the periodontitis groups compared to the control group, fractal analysis did not demonstrate any periodontitis-associated changes of bone tra-beculationin diabetes at any stage of periodontitis. Furthermore, there was no significant association between fractal analysis values and age, sex, clinical attachment, and bone loss. [ABSTRACT FROM AUTHOR]

The biggest challenge during periodontal regeneration in the anterior region is the prevention of soft tissue recession. Minimally invasive surgeries, particularly papilla preservation techniques and soft tissue augmentation, may significantly reduce such postoperative soft tissue recession. This article presents the vestibular incision subperiosteal tunnel access (VISTA) approach for periodontal regeneration in the anterior region. A subperiosteal tunnel prepared from a single vertical vestibular incision adjacent to the defect is used for debridement, application of enamel matrix derivative, defect grafting with corticocancellous tuberosity bone, and insertion of the connective tissue graft. Evaluation of six cases with up to 6 years of follow-up showed improvements in all clinical parameters. The probing pocket depth improved from 8.2 ± 0.75 mm initially to 2.7 ± 0.52 mm at follow-up, clinical attachment level improved from 8.5 ± 0.83 mm initially to 2.7 ± 0.52 mm at follow-up, and midfacial gingival recession of 1 mm at two sites was corrected. The papillae were stable at all sites, with an average distance of 4.8 mm from the incisal edge to the papilla tip. This technique seems to be a promising approach for achieving both esthetic and functional goals of periodontal regenerative surgery. However, experience in performing microsurgeries and harvesting tuberosity tissues may be a limitation. [ABSTRACT FROM AUTHOR]

Purpose: To examine the stresses caused by different All-on-4 surgical techniques—conventional, a combination of monocortical and bicortical, bicortical, and nasal floor elevation—on the implant and the surrounding bone using 3D finite element analysis (FEA). Materials and Methods: A 3D bone model of the atrophic maxilla was created based on CT imaging of the fully edentulous adult patient. All implants used in the models were 4 mm in diameter, and the length was 13 mm in the anterior and 15 mm in the posterior. Implants were applied to four different atrophic maxillary models with the All-on-4 technique: anterior and posterior monocortical implants in the first model, anterior monocortical and posterior bicortical in the second model, anterior and posterior bicortical in the third model, and anterior and posterior bicortical with nasal floor elevation in the fourth model. Eight linear analyses were performed by applying force from both vertical and 45-degree oblique directions to the four models prepared in our study. Results: When the cortical and cancellous bone around the anterior implants was examined, it was observed that the oblique and vertical loading conditions and the stresses around the implant were similar in all models. When the posterior implants were examined, model 1 (ie, anterior and posterior monocortical implants) showed the greatest oblique compression, vertical compression, and vertical tension forces. According to the Von Mises stress (VMS) analysis results for anterior and posterior implants, higher values were observed in model 1 compared to models 3 and 4 under oblique and vertical forces. It was observed that bicortical placement of the implants reduced the stresses on the bone and implant-abutment system but had no significant effect on the stress on the bar. Conclusions: According to the results of our study, in the All-on-4 technique, bicortical placement of the implants reduced the stresses on the bone and implant when the anatomical limitations allowed. In addition, nasal floor elevation can be applied in the atrophic maxilla in appropriate indications. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a significant global health issue and often involves CKD-mineral and bone disorder (MBD) and sarcopenia. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. PAI-1 has been implicated in the pathogenesis of osteoporosis and muscle wasting induced by inflammatory conditions. However, the roles of PAI-1 in CKD-MBD and sarcopenia remain unknown. Therefore, the present study investigated the roles of PAI-1 in bone loss and muscle wasting induced by adenine in PAI-1-deficient mice. CKD was induced in PAI-1+/+ and PAI-1-/- mice by administration of adenine for ten weeks. Muscle wasting was assessed by grip strength test, quantitative computed tomography (CT) analysis and muscle weight measurement. Osteoporosis was assessed by micro-CT analysis of femoral microstructural parameters. PAI-1 deficiency did not affect adenine-induced decreases in body weight and food intake or renal dysfunction in male or female mice. PAI-1 deficiency also did not affect adenine-induced decreases in grip strength, muscle mass in the lower limbs, or the tissue weights of the gastrocnemius, soleus, and tibialis anterior muscles in male or female mice. PAI-1 deficiency aggravated trabecular bone loss in CKD-induced male mice, but significantly increased trabecular bone in CKD-induced female mice. On the other hand, PAI-1 deficiency did not affect cortical bone loss in CKD-induced mice. In conclusion, PAI-1 is not critical for the pathophysiology of CKD-MBD or CKD-induced sarcopenia in mice. However, PAI-1 may be partly related to bone metabolism in trabecular bone in the CKD state with sex differences. [ABSTRACT FROM AUTHOR]

Purpose: The difference of Hounsfield Unit (HU) value in different regions of L3 vertebra in middle-aged and elderly patients with lumbar degeneration diseases (LDD) was analyzed. To investigate the influence of proliferative tissue on HU value of cancellous bone and its correlation with bone mineral density (BMD). Methods: The medical records of middle-aged and elderly patients with LDD in our hospital from December 2020 to December 2023 were retrospectively analyzed. The patients were divided into osteophyte group and no-osteophyte group according to the presence or absence of osteophyte formation on lumbar spine X-ray. In osteophyte group, cancellous bone HU value, containing cortical bone overall HU value and containing osteophyte overall HU value in L3 vertebra were measured on the lumbar CT cross-section. In no-osteophyte group, only the cancellous bone HU value and the containing cortical bone overall HU value were measured. Differences in HU value in different regions of the L3 vertebral body were compared within and between groups of middle-aged and elderly patients with LDD, respectively. To investigate its effect on cancellous bone HU measurements and to do a correlation analysis with patients' BMD. Results: A total of 115 patients with LDD were included in this study, including 65 males and 50 females, with an average age of 67.83 ± 6.59 years. The results of the study showed no statistical differences in age (P = 0.15), gender (P = 0.57), smoking (P = 0.88), drinking history (P = 0.76), medical history (P > 0.05) and BMI(P = 0.29) between the two groups. In osteophyte group, the mean cancellous bone HU value was 98.00 ± 25.50 HU, the containing cortical bone overall HU value was 189.02 ± 46.18 HU, and the containing osteophyte overall HU value was 232.69 ± 56.01 HU. The overall HU values containing cortical bone and containing osteophyte were significantly higher than cancellous bone HU value (P < 0.001). In no-osteophyte group, the mean cancellous bone HU value was 102.04 ± 19.64 HU, and the containing cortical bone overall HU value was 175.00 ± 28.97 HU, which was statistically significantly different (P < 0.001). There was no significant difference in cancellous bone HU value and the containing cortical bone overall HU value between the two groups (P > 0.05). The results of the Pearson correlation analysis showed a significant correlation between the cancellous bone HU value of the L3 vertebrae and the QCT BMD value of the patients (r = 0.95, P < 0.001). However, there was no significant correlation between containing cortical bone overall HU value and containing osteophyte overall HU value and the patient's QCT BMD value (P > 0.05). Conclusions: Vertebral HU value is an alternative measurement that effectively reflects the patient's BMD. In middle-aged and elderly LDD patients, HU values in different areas of L3 vertebra are significantly different, and hyperplastic tissues such as cortical bone and osteophytes may exponentially lead to higher HU value in patients. Compared with other measurement areas, vertebral cancellous bone HU value have the advantage of accurately assessing patients' BMD. [ABSTRACT FROM AUTHOR]

Introduction We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. Materials and Methods Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. Results MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. Conclusion A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats. [ABSTRACT FROM AUTHOR]

Objective: In addition to the surface hemorrhage of cancellous bone after large‐area osteotomy, the intramedullary hemorrhage after the reamed knee joint is also a major cause of postoperative bleeding after total knee arthroplasty (TKA). This study evaluated the efficacy and safety of bone wax application at different time points of prone hemorrhage to reduce perioperative blood loss. Methods: From August 2023 to December 2023, 150 patients undergoing primary unilateral TKA were included in this prospective, randomized controlled trial, patients were randomly divided into three groups: group A, after autogenous osteotomy plug was used to fill the femoral medullary cavity, the residual space was sealed with bone wax and the exposed cancellous bone surface around the prosthesis was coated with bone wax after the prosthesis adhesion; group B, only the exposed cancellous bone surface around the prosthesis was coated with bone wax; and group C, no bone wax was used. The primary outcome was total perioperative blood loss. Secondary outcomes included occult blood loss, postoperative hemoglobin reduction, blood transfusion rate, lower limb diameter, and knee function, while length of hospital stay was recorded. Tertiary outcomes included the incidence of postoperative related adverse events. Results: The total blood loss in group A (551.5 ± 224.5 mL) and group B (656.3 ± 267.7 mL) was significantly lower than that in group C (755.3 ± 248.3 ml, p < 0.001), and the total blood loss in group A was also lower than that in group B (p < 0.05). There were also significant differences in the reduction of hemoglobin level and hidden blood loss among the three groups (p < 0.05). However, there was no significant improvement in postoperative lower limb swelling, knee joint activity and hospitalization time; there was no significant difference in the incidence of complications such as thromboembolism. Conclusion: The use of bone wax in TKA can safely and effectively reduce perioperative blood loss and hemoglobin drop rate, and multiple use at time points during the operation when blood loss is prone to occur can produce more significant hemostatic effect. [ABSTRACT FROM AUTHOR]

Evidence acquired in the past years highlighted the high complexity of Neanderthal subsistence strategies in terms of the spectrum of exploited species (mammals, birds, aquatic resources). However, in many sites diet was mainly focused on the acquisition and processing of large and medium-sized ungulates. In these cases, the evaluation of killing profiles and skeletal frequencies has allowed to highlight behavioural variability among Mousterian populations living in different geographical areas. In the frame of these studies, zooarchaeology and taphonomy of the Middle Palaeolithic phases (MIS 4/MIS 3) from the external deposit of Grotta di Santa Croce (Apulia, southern Italy) are presented in this paper. Faunal assemblage is almost exclusively composed of horse and aurochs remains. The sample, which is not altered by carnivore activities, mainly consists of intensively fractured limb bone shafts and isolated teeth. Epiphyses, tarsal/carpal bones, and phalanges are quite rare, as well as unidentified spongy bone fragments. Analysis of tooth eruption and wear points to the exploitation of adult individuals, rather than juveniles and sub-adults. Body part profiles, as well as mortality ones point to a specific hunting behaviour that may reflect particular nutritional needs. The hypothesis of an intense exploitation of fats is discussed. [ABSTRACT FROM AUTHOR]

Bone formation is tightly modulated by genetically encoded molecular proteins that interact to regulate cellular differentiation and secretion of bony matrix. Many transcription factors are known to coordinate these events by controlling gene transcription within networks. However, not all factors involved are known. Here, we identified a novel function for Zinc Finger Homeobox 3 (Zfhx3), a gene encoding a transcription factor, as a regulator of bone metabolism. We knocked out Zfhx3 conditionally in mice in either chondrocytes or osteoblasts and characterized their bones by micro-CT in 12-week-old mice. We observed a negative effect in linear bone growth in both knockout mice but reduced bone mass only in mice with Zfhx3 deleted in osteoblasts. Loss of Zfhx3 expression in osteoblasts affected trabecular bone mass in femurs and vertebrae in both sexes but influenced cortical bone volume fraction only in females. Moreover, transcriptional analysis of femoral bones in osteoblast Zfhx3 conditional knockout mice revealed a reduced expression of osteoblast genes, and histological evaluation of trabecular bones suggests that Zfhx3 causes changes in bone formation and not resorption. The loss of Zfhx3 causes reductions in trabecular bone area and osteoid volume, but no changes in the expression of osteoclast differentiation markers or number of TRAP stained osteoclasts. These studies introduce Zfhx3 as a relevant factor toward understanding gene regulatory networks that control bone formation and development of peak bone mass. [ABSTRACT FROM AUTHOR]

A bone bruise is generated by a bony collision that could occur when the anterior cruciate ligament (ACL) is injured, and its pattern reflects the injury mechanism and skeletal maturity. Thus, the bone bruise pattern is useful to predict a subject-specific injury mechanism, although the sensitivity and/or effect of the material property and the knee position at injury is still unclear. The objective of the present study was to determine the effect of the material property and knee position on the bone bruise pattern in skeletally mature and immature subjects using finite element analysis. Finite element models were created from a magnetic resonance (MR) image in the sagittal plane of a skeletally mature (25 y. o.) and immature (9 y. o.) male subject. The femur and tibia were collided at 2 m/s to simulate the impact trauma and determine the maximum principal stress. The analysis was performed at 15, 30, and 45 deg of knee flexion, and neutral, 10 mm anterior and posterior translated position at each knee flexion angle. Although high stress was distributed toward the metaphysis area in the mature model, the stress did not cross the growth plate in the immature model. The size of the stress area was larger in the mature model than those in the immature model. The location of the stress area changed depending on the joint position. Young's modulus of cartilage and trabecular bone also affected the location of the stress area. The Young's modulus for the cartilage affected peak stress during impact, while the size of the stress area had almost no change. These results indicate that the bone bruise pattern is strongly associated with subject-specific parameters. In addition, the bone bruise pattern was affected not only by knee position but also by tissue qualities. In conclusion, although the bone bruise distribution was generally called footprint of the injury, the combined evaluation of the quality of the structure and the bone bruise distribution is necessary for properly diagnosing tissue injury based on the MR imaging. [ABSTRACT FROM AUTHOR]

In the past decade, the transfibular approach to Total Ankle Replacement (TAR) has emerged as an alternative to anterior approach with reduced bone resection. The purpose of this systematic review is to report survival, complications, and reoperation rates of transfibular TAR. We conducted a systematic search of studies that evaluated complications, reoperations, and survival of transfibular TAR following PRISMA guidelines across PubMed, Scopus and Web of Science. Our review included data from 12 cohorts, comprising 919 patients across 7 countries, with an average age of 62 years (59% posttraumatic). Over an average follow-up period of 3 years, adverse events occurred in 23% of cases, with 18% requiring surgical reintervention, mostly due to hardware removal. The survival rate of the transfibular TAR metal components was 97% at the final follow-up. Transfibular TAR demonstrates a 97% survival rate at a 3-year follow-up. Level II [ABSTRACT FROM AUTHOR]

The primary component of natural bone minerals, hydroxyapatite (HA), has been the subject of research on materials for bone implants. Sintered HA scaffolds, on the other hand, degrade slowly after implantation and exhibit a high degree of crystallization at high temperatures, making it challenging to match the rate at which new bone grows. In this study, the benefit of self-curing calcium phosphate bone cement was employed to create porous apatite scaffolds without sintering. The lamellar pore structure was created by directional freeze-casting, and the enhanced specific surface area aided the in-situ hydration process. The crystallinity of sinterless porous apatite scaffolds diminishes when the TTCP and DCPD molar ratios drop. When the molar ratio is adjusted to 1:2.25, the crystallinity of the fabricated scaffold is reduced to 63.99 %, and 10.21 % can be degraded in 30 days. The degradation of porous scaffolds in simulated body fluids mainly depends on the rapid dissolution and transformation of solid phase powders in the early hydration reaction and the slow diffusion of the apatite in the later stage. The compressive strength of the porous scaffold is 5.3 MPa and its elastic modulus is 0.68 GPa. After 14 days of degradation, the compressive strength was 4.0 MPa and the elastic modulus was 0.64 GPa, which was still within the applicable range of cancellous bone repair. It has a promising application prospect as a substitute scaffold for absorbable cancellous bone. [ABSTRACT FROM AUTHOR]

Background: The adult human skeleton is composed of cortical and cancellous bone. The proportions of these two types of bone tissue differ in various parts of the skeleton. The aim of this cross-sectional study was to quantify the determinants of bone mineral density (BMD) and bone mineral content in various regions of interest (ROIs) in smokers and never-smokers. Methods: In this study, 4,332 bone scans of three regions of interest (ROIs) were analyzed: the forearm (distal and proximal), femur, and lumbar spine. Body composition and bone parameters were measured using dual-energy X-ray absorptiometry. Smoking was measured using the Global Adult Tobacco Survey questionnaire. Body mass index (BMI) was calculated, and physical activity (PA) was characterized by the metabolic equivalent of task (MET). Results: Among women, the interaction between PA (positive ß coefficient) and smoking (negative ß coefficient) was a significant predictor of BMD in the distal and proximal forearm (adj. R2 = 0.40 and R2 = 0.58; p < 0.001). The interaction of three variables--age, smoking (negative ß), and MET (positive ß)--was significant for total hip BMD (adj. R2 = 0.54; p < 0.001). The interaction between BMI and MET (positive ß) and smoking (negative ß) was significant for BMD in the lumbar spine (adj. R2 = 0.62; p < 0.001). In men, the interaction between MET (positive ß) and smoking (negative ß) was significant for BMD in the forearm and lumbar spine (adj. R2 = 0.44, R2 = 0.46, and R2 = 0.49; p < 0.01). Smoking alone was a significant negative predictor of total hip BMD (adj. R2 = 0.34; p < 0.001). Conclusion: Among both women and men, never-smokers had significantly better bone parameters than smokers. Smoking was a significant negative predictor for BMD in the various ROIs in both women and men. Physical activity was a significant positive predictor of BMD, with a strong association with bone parameters. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of the All-on-4 design and 4 alternative implant-supported fixed prosthesis designs on stress distribution in implants, peri-implant bone, and prosthetic framework in the edentulous mandible under different loading conditions using three-dimensional finite element analysis (3D-FEA).Five different experimental finite element models (Model A (unsplinted 6), Model B (splinted 6), Model C (All-on-4), Model D (axial; 2 anterior, 2 posterior), and Model E (4 interforaminal)) were created. Three different loading conditions were applied (canine loading, unilateral I-loading, and unilateral II-loading). The highest minimum (Pmin) and the maximum (Pmax) principal stress values were acquired for cortical and trabecular bones; the highest von Mises (mvM) stress values were obtained for implants and metal frameworks. Model B and Model D showed the most favorable stress distribution. The All-on-4 design (Model C) also showed acceptable stress values close to those of Model B and Model D in the cortical and trabecular bones. In accordance with the stress values in the bone structure, the lowest stress values were measured in the implants and Co-Cr framework in Model B and Model D. The highest stress values in all structures were measured for unilateral loading- II, while the lowest values were found for canine loading. It was concluded that Model B and Model D experimental models showed better biomechanical performance in all structures. Furthermore, the use of a splinted framework, avoiding cantilevers, results in lower stress transmission. On the other hand, canine loading and unilateral loading-I exhibited the best loading conditions. [ABSTRACT FROM AUTHOR]

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone. Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR. Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation. In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high‐fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high‐fat high‐sugar (HFHS) diet would promote spontaneous osteoarthritis‐related cartilage and bone changes in 1‐year‐old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow‐fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation. Male and female offspring were weaned onto a chow diet, raised to 1 year of age, and evaluated for cartilage and bone changes indicative of OA. However, offspring did not show early signs of OA as measured by histological Mankin scoring, mechanical testing of the pericellular matrix, histological synovitis scoring, or subchondral bone thickening as measured by microcomputed Tomography. On the other hand, male offspring from HFHS‐fed dams had reduced trabecular bone quality in the tibial metaphysis and decreased cortical thickness. Although maternal HFHS diet did not impact trabecular or cortical bone quality in tibias of female offspring, the radii of these animals had decreased cortical thickness, increased medullary area, and impaired breaking strength compared to those of control‐fed dams. Finally, we evaluated bone quality and strength in male and female F2 offspring and found that the grandmaternal diet modestly impacted radial bone geometry but not strength. Together these results suggest that maternal HFHS diet impairs F1 offspring skeletal integrity in a sex and bone site‐specific manner. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a major health concern for postmenopausal women, and the effect of simvastatin (Sim) on bone metabolism is controversial. This study aimed to investigate the effect of simvastatin on the bone microstructure and bone mechanical properties in ovariectomized (OVX) mice. Methods: 24 female C57BL/6J mice (8-week-old) were randomly allocated into three groups including the OVX + Sim group, the OVX group and the control group. At 8 weeks after operation, the L4 vertebral bones were dissected completely for micro-Computed Tomography (micro-CT) scanning and micro-finite element analysis (µFEA). The differences between three groups were compared using ANOVA with a LSD correction, and the relationship between bone microstructure and mechanical properties was analyzed using linear regression. Results: Bone volume fraction, trabecular number, connectivity density and trabecular tissue mineral density in the OVX + Sim group were significantly higher than those in the OVX group (P < 0.05). For the mechanical properties detected via µFEA, the OVX + Sim group had lower total deformation, equivalent elastic strain and equivalent stress compared to the OVX group (P < 0.05). In the three groups, the mechanical parameters were significantly correlated with bone volume fraction and trabecular bone mineral density. Conclusions: The findings suggested that simvastatin had a potential role in the treatment of osteoporosis. The results of this study could guide future research on simvastatin and support the development of simvastatin-based treatments to improve bone health. [ABSTRACT FROM AUTHOR]

Three-dimensional correlative multimodal and multiscale imaging is an emerging method for investigating the complex hierarchical structure of biological materials such as bone. This approach synthesizes images acquired across multiple length scales, for the same region of interest, to provide a comprehensive view of the material structure of a sample. Here, we develop a workflow for the structural analysis of human trabecular bone using a femtosecond laser to produce a precise grid to facilitate correlation between imaging modalities and identification of structures of interest, in this case, a single trabecula within a volume of trabecular bone. Through such image registration, high resolution X-ray microscopy imaging revealed fine architectural details, including the cement sheath and bone cell lacunae of the selected bone trabecula. The selected bone volume was exposed with a combination of manual polishing and site-specific femtosecond laser ablation and then examined with plasma focused ion beam-scanning electron microscopy. This reliable and versatile correlation approach has the potential to be applied to a variety of biological tissues and traditional engineered materials. The proposed workflow has the enhanced capability for generating highly resolved and broadly contextualized structural data for a better understanding of the architectural features of a material spanning its macroscopic to nanoscopic levels. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. Methods: In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. Results: There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p < 0.001), and had no significant effect on BV/TV in medial and lateral femoral condyles (MT, LT). Similarly, BPs could significantly affect the effective modulus in IT (sham-OVX vs. BP, p < 0.001), and had no significant difference in MT and LT. In addition, the structural parameters and effective modulus showed a good linear correlation. Conclusion: In a short time, the effects of BP intervention and osteoporosis on cortical bone were not obvious. The effects of BP on trabecular bone in non-main weight-bearing area (IT) were valuable, while for osteoporosis, the main weight-bearing area (MT, LT) may improve the structural quality and mechanical strength of trabecular bone through exercise compensation. [ABSTRACT FROM AUTHOR]

Neural EGFL like 1 (NELL-1), is a secreted glycoprotein and stimulates osteogenic cell differentiation and bone mineralization. This study aimed to explore the relationship between NELL-1 and Trabecular Bone Score (TBS) as a novel tool for the evaluation of osteoporosis in an elderly population-based cohort study in Iran. A single-locus analysis was performed on TBS using data from 2,071 participants in the Bushehr Elderly Health (BEH) Program. The study investigated 376 independent single nucleotide polymorphisms (SNPs) within the NELL-1 on chromosome 11p15.1. The association between SNPs and the mean TBS L1 to L4 was analyzed through an additive model. Significant variants in the additive model (PFDR<0.05) were further examined within dominant, recessive, over-dominant, and co-dominant models. Multiple linear regression was employed to assess the relationship between the genetic risk score (GRS) derived from significant SNPs and TBS. Three SNPs within the NELL-1 showed a statistically significant association with TBS after adjusting for age and sex. The associations for rs1901945 (β = 0.013, PFDR = 0.0007), rs1584851 (β = -0.011, PFDR = 0.0003), and rs58028601 (β = 0.011, PFDR = 0.0003) were significant in the additive model. Additionally, significant results were observed for rs1901945 and rs58028601 in the dominant model (P<0.05). The GRS showed a statistically significant relationship with TBS, considering adjustments for age, sex, Body Mass Index, type 2 diabetes, and smoking (β = 0.077, P = 1.7×10−5). This study highlights the association of NELL-1 with TBS, underscoring its potential as a candidate for further research and personalized medicine concerning the impact of this gene on bone quality. [ABSTRACT FROM AUTHOR]

The development of synthetic bone substitutes that equal or exceed the efficacy of autologous graft remains challenging. In this study, a rat calvarial defect model was used as a reference to investigate the influence of composition and architecture of 3D-printed cement, with or without bioactives, on tissue regeneration. Printable cement pastes were formulated by combining hyaluronic acid and cement precursors. Cementitious scaffolds were printed with 3 different patterns. After 7 weeks of implantation with or without bone marrow, multiparametric qualitative and quantitative assessments were performed using µCT, SEM, and histology. None of the set-up strategies was as efficient as autologous cancellous bone graft to repair calvarial defects. Nonetheless, the presence of scaffold improved the skull vault closure, particularly when the scaffold was soaked in total bone marrow before implantation. No significant effect of scaffold macro-architecture was observed on tissue mineralization. Magnesium phosphate-based scaffolds (MgP) seemed to induce higher bone formation than their calcium-phosphate-based counterparts. They also displayed a quicker biodegradation and sparse remaining material was found after 7 weeks of implantation. Although further improvements are required to reach clinical settings, this study demonstrated the potential of organo-mineral cements for bone regeneration and highlighted the peculiar properties of MgP-based cements. [ABSTRACT FROM AUTHOR]

GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF‐β signaling. In this study, we investigated the role of TGF‐β‐signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO. Treatment of GorabPrx1 conditional knockouts with the TGF‐β neutralizing antibody 1D11 rescued the trabecular bone loss, indicating that TGF‐β overactivation causes osteoporosis in GO. Using an inducible knockout system, we demonstrated that TGF‐β dysregulation was not a cell‐intrinsic effect of GORAB inactivation, but a consequence of a disorganized extracellular matrix. Enhanced TGF‐β signaling caused elevated Nox4 expression in GorabPrx1 mutants and in GO patients' fibroblasts, resulting in overproduction of mitochondrial superoxide. The resulting oxidative stress was detected in GORAB null cells and also in wildtype bystander cells. The same effect was observed in zebrafish after TALEN‐mediated gorab inactivation, indicating that the pathway is evolutionarily conserved. Treating GorabPrx1 mutants with the antioxidant N‐acetylcysteine ameliorated the osteoporosis phenotype. TGF‐β induced oxidative stress coincided with accumulation of DNA damage and elevated expression of senescence markers. Inactivation of Cdkn2a in the GorabPrx1 rescued the osteoporosis phenotype. Reduced colony formation and altered subpopulations of bone marrow stromal cells were normalized upon inactivation of Cdkn2a, thus further demonstrating the relevance of cellular senescence in the pathogenesis. Our results shed light on the causative role of a TGF‐β‐Nox4‐senescence axis and therapeutic strategies for GO. [ABSTRACT FROM AUTHOR]

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis. [ABSTRACT FROM AUTHOR]

Advanced laboratory methods play a crucial role in bone research, allowing researchers and scientists to study the complex biology and nature of the skeleton. Dual-energy X-ray absorptiometry (DXA) is a non-invasive method of measuring bone mass, which is an important parameter for the diagnosis and treatment of several bone diseases. Micro-computed tomography (μCT) is a very high-resolution technique that can be used to investigate the 3D microstructure of trabecular bone. Dynamic bone histomorphometry is used to assess histological indices of bone formation and resorption using fluorochromes embedded into newly formed bone. Mechanical testing is used to measure bone strength and stiffness, providing important information about bone quality and fracture risk. All these methods are widely used in preclinical in vivo studies using rodents and in most clinical studies. Therefore, it is important for both researchers and scientists within the field of bone biology, and those in neighboring fields, to be familiar with their use, strengths, limitations, and important technical aspects. Several guidelines and protocols about the topic have been published, but are very exhaustive. The present review aimed to provide instructions for early-career researchers and outline important concepts and technical aspects of DXA, μCT, dynamic bone histomorphometry, and mechanical testing in bone research. [ABSTRACT FROM AUTHOR]

Osteosarcopenia is a prevalent geriatric disease with a significantly increased risk of adverse outcomes than osteoporosis or sarcopenia alone. Identification of older adults with osteosarcopenia using High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) could allow better clinical decision making. This study aimed to explore the feasibility of HR-pQCT to differentiate osteoporosis, sarcopenia, and osteosarcopenia in older adults, with a primary outcome to derive a model to distinguish older adults with osteosarcopenia from those with low bone mineral density only, and to examine important HR-pQCT parameters associated with osteosarcopenia. This was a cross-sectional study involving 628 community-dwelling Chinese adults aged ≥ 40. Subjects were assessed by dual energy X-ray absorptiometry (DXA) for osteopenia/osteoporosis and sarcopenia using the Asian Working Group for Sarcopenia definition; then grouped into healthy, osteopenia/osteoporosis, sarcopenia, and osteosarcopenia groups. A series of regression analyses and other statistical tests were performed to derive the model. HR-pQCT showed the ability to discriminate older adults with osteosarcopenia from those with osteopenia/osteoporosis only. Cross-validation of our derived model correctly classified 77.0% of the cases with good diagnostic power and showed a sensitivity of 76.0% and specificity of 77.6% (Youden index = 0.54; AUC = 0.79, p < 0.001). Analysis showed trabecular volumetric bone density and cortical periosteal perimeter were important and sensitive parameters in discriminating osteosarcopenia from osteopenia/osteoporosis subjects. These findings demonstrated that HR-pQCT is a viable and effective screening method for differentiating osteosarcopenia from low bone mineral density alone without the need to carry out multiple assessments for osteosarcopenia, especially for case-finding purposes. This could facilitate the decision of a follow-up and the management of these frail older adults to ensure they receive timely therapeutic interventions to minimise the associated risks. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tissue engineering seeks to improve, maintain, or replace the biological functions of damaged organs or tissues with biological substitutes such as the development of scaffolds. In the case of bone tissue, they must have excellent mechanical properties like native bone. OBJECTIVE: In this work, three geometric models were designed for scaffolds with different structure lattices and porosity that could be biomechanically suitable and support cell growth for trabecular bone replacement applications in tissue engineering and regenerative medicine to the proximal femur area. METHODS: Geometries were designed using computer-aided design (CAD) software and evaluated using finite element analysis in compression tests. Three loads were considered according to the daily activity: 1177 N for slow walking, 2060 N for fast walking, and 245.25 N for a person in a bipedal position. All these loads for an adult weight of 75 kg. For each of them, three biomaterials were assigned: two polymers (poly-glycolic acid (PGA) and poly-lactic acid (PLA)) and one mineral (hydroxyapatite (HA)). 54 tests were performed: 27 for each of the tests. RESULTS: The results showed Young's modulus (E) between 1 and 4 GPa. CONCLUSION: If the resultant E is in the range of 0.1 to 5 GPa, the biomaterial is considered an appropriate alternative for the trabecular bone which is the main component of the proximal bone. However, for the models applied in this study, the best option is the poly-lactic acid which will allow absorbing the acting loads. [ABSTRACT FROM AUTHOR]

ZC4H2 encodes a C4H2-type zinc finger protein, mutations of which lead to a spectrum of diseases known as ZC4H2 associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear. Here, we showed that ZC4H2 is expressed in the developing bones in mice. ZC4H2 knockout mice were neonatal-lethal and smaller in size, with reduced calcification of long bones. Upon induced loss of ZC4H2 postnatally, the femoral bones developed an osteoporosis-like phenotype, with reduced bone mineral density, bone-volume fraction, and trabecular bone number. Knockdown of ZC4H2 showed no clear effect on the expression of osteogenic differentiation genes in in vitro models using mesenchymal stem cells. Interestingly, ZC4H2 knockdown significantly enhanced osteoclast differentiation and bone resorption in induced bone marrow-derived macrophages. We further confirmed that the number of osteoclasts in the long bone of ZC4H2 knockout mice was increased, as well as the expression of the serum bone resorption/osteoporosis marker CTX-1. Our study unveils a new role of ZC4H2 in osteoclast differentiation and bone development, providing new clues on the pathology of ZARD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Obesity can be associated with impaired growth hormone (GH) secretion, with possible negative repercussions on bone health. We aimed to investigate the relationships between GH secretory capacity, evaluated with GHRH + arginine stimulation test, and bone parameters, assessed with a dual-energy X-ray absorptiometer, in a population of adult female patients affected by overweight and obesity. Methods: We assessed 276 women affected by overweight or obesity referred to the High-Specialization Center for the Care of Obesity, Umberto I Polyclinic, between 2014 and 2019 with signs or symptoms of growth hormone deficiency (GHD). Results: A total of 97 patients were diagnosed with GHD, and 179 patients with normal GH secretion were considered our control group. GHD patients showed a significantly reduced trabecular bone score (TBS) (p = 0.01). Bone quality parameters corrected for body mass index (BMI) had a positive and significant linear correlation with stimulated GH secretory capacity. Conclusions: In conclusion, bone quality, evaluated by TBS and hip structural analysis, correlates with GH-stimulated secretory capacity. GHD may act as an additive factor in the alteration of bone microarchitecture in patients affected by obesity, who are already at a higher risk of fractures. [ABSTRACT FROM AUTHOR]

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration. [ABSTRACT FROM AUTHOR]

Small‐angle‐scattering tensor tomography is a technique for studying anisotropic nanostructures of millimetre‐sized samples in a volume‐resolved manner. It requires the acquisition of data through repeated tomographic rotations about an axis which is subjected to a series of tilts. The tilt that can be achieved with a typical setup is geometrically constrained, which leads to limits in the set of directions from which the different parts of the reciprocal space map can be probed. Here, we characterize the impact of this limitation on reconstructions in terms of the missing wedge problem of tomography, by treating the problem of tensor tomography as the reconstruction of a three‐dimensional field of functions on the unit sphere, represented by a grid of Gaussian radial basis functions. We then devise an acquisition scheme to obtain complete data by remounting the sample, which we apply to a sample of human trabecular bone. Performing tensor tomographic reconstructions of limited data sets as well as the complete data set, we further investigate and validate the missing wedge problem by investigating reconstruction errors due to data incompleteness across both real and reciprocal space. Finally, we carry out an analysis of orientations and derived scalar quantities, to quantify the impact of this missing wedge problem on a typical tensor tomographic analysis. We conclude that the effects of data incompleteness are consistent with the predicted impact of the missing wedge problem, and that the impact on tensor tomographic analysis is appreciable but limited, especially if precautions are taken. In particular, there is only limited impact on the means and relative anisotropies of the reconstructed reciprocal space maps. [ABSTRACT FROM AUTHOR]

Changes in bone microarchitecture resulting from chronic physical stress such as that experienced during U.S. Army Basic Combat Training (BCT) underscore its adaptive potential. There is a need for noninvasive biomarkers of adaptive bone formation that can be obtained at scale in real-world settings. Differential mass spectrometry (dMS), a label-free quantitative proteomics technique, may provide useful information about bone adaptation based on the proteomic features of urine. Purpose: The purpose of this study is to optimize a dMS-based urinary proteomic technique and evaluate the relationship between urinary proteome content and adaptive changes in bone microarchitecture during BCT. Methods: Urinary proteomes were analyzed with an optimized dMS technique in two groups of 13 recruits (N = 26) at the beginning (Pre) and end (Post) of BCT. Matched by age (21 ± 4 yr), sex (16 W), and baseline tibial trabecular bone volume fractions (Tb.BV/TV), these groups were distinguished by themost substantial (High) and minimal (Low) improvements in Tb.BV/TV. Differential protein expression was analyzed with mixed permutation ANOVA and false discovery proportion-based adjustment for multiple comparisons. Results: Tibial Tb.BV/TV increased from pre- to post-BCT in High (3.30 ± 1.64%, P < 0.0001) but not Low (-0.35 ± 1.25%, P = 0.4707). The optimized dMS technique identified 10,431 peptides from 1368 protein groups that represented 165 integrative biological processes. Seventy-four urinary proteins changed from pre- to post-BCT (P = 0.0019), and neutrophil-mediated immunity was the most prominent ontology. Two proteins (immunoglobulin heavy constant gamma 4 and C-type lectin domain family 4 member G) differed from pre- to post-BCT in High and Low (P = 0.0006). Conclusions: The dMS technique can identify more than 1000 urinary proteins. At least 74 proteins are responsive to BCT, and other principally immune system--related proteins show differential expression patterns that coincide with adaptive bone formation. [ABSTRACT FROM AUTHOR]

An association of eighteen coprolites (specimens 01–18) and one isolated coprolite (specimen 209,210) were found in a vertebrate fossil-rich paleosol at the Gratkorn site (south-eastern Austria; late Middle Miocene). The specimens consist mostly of calcium phosphate (apatite) and a matrix formed by microglobules. Coprolites 01–18 show cylindrical and spherical morphologies and are considerably smaller than the tube-shaped specimen 209,210, in which no inclusions were observed. In contrast, coprolites 01–18 contain numerous, highly altered bone fragments (sub-mm-sized long bones and several mm-sized trabecular bone remains) as well as hair imprints, plant detritus and palynomorphs. Based on composition, morphology, size, microstructure, and inclusions, and considering the body fossil record of this site, we assume the hyaenid Protictitherium and the barbourofelid Albanosmilus, as producers of coprolites 01–18 and 209,210, respectively. The preserved bone remains in specimens 01–18 suggest that Protictitherium fed on small vertebrates, but possibly also cracked bones of medium-sized animals. The hair imprints found were either from the hyaenid itself or its prey, while the plant material was probably ingested accidentally. The lack of inclusions in specimen 209,210 is related to the presumably hypercarnivorous diet of Albanosmilus, which was certainly the apex predator in this biome. [ABSTRACT FROM AUTHOR]

Increased fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD) by DXA. Advanced glycation end-products (AGEs) have been implicated in the increased fracture risk in T1D, yet recent publications question this. To test the hypothesis that enzymatic collagen cross-links rather than AGEs correlate with fracture incidence in T1D, we analyzed iliac crest biopsies from sex-matched, fracturing T1D patients (N = 5; T1DFx), 6 non-fracturing T1D patients (T1DNoFx), and 6 healthy subjects, by Raman microspectroscopy as a function of tissue age (based on double fluorescent labels), in intracortical and trabecular bone, to determine pyridinoline (Pyd), ε-N-Carboxymethyl-L-lysine, and pentosidine (PEN)). There were no differences in the clinical characteristics between the T1DFx and T1DNoFx groups. At trabecular forming surfaces, T1DFx patients had higher PEN and Pyd content compared to T1DNoFx ones. Previous studies have shown that elevated PEN does not necessarily correlate with fracture incidence in postmenopausal, long-term T1D patients. On the other hand, the elevated Pyd content in the T1DFx patients would be consistent with published studies showing a significant correlation between elevated trivalent enzymatic collagen cross-links and fracture occurrence independent of BMD. Collagen fibers with high Pyd content are more brittle. Thus, a plausible suggestion is that it is the enzymatic collagen cross-links that either by themselves or in combination with the adverse effects of increased AGE accumulation that result in fragility fracture in T1D. [ABSTRACT FROM AUTHOR]

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography to that of controls after Plasmodium yoelii non-lethal infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC, precursors resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, insulin-like growth factor-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions. [ABSTRACT FROM AUTHOR]

Summary: Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. Purpose: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. Methods: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. Results: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. Conclusion: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Bone diseases deteriorate the microstructure of bone tissue. Optical-resolution photoacoustic microscopy (OR-PAM) enables high spatial resolution of imaging bone tissues. However, the spatiotemporal trade-off limits the application of OR-PAM. The purpose of this study was to improve the quality of OR-PAM images without sacrificing temporal resolution. In this study, we proposed the Photoacoustic Dense Attention U-Net (PADA U-Net) model, which was used for reconstructing full-scanning images from under-sampled images. Thereby, this approach breaks the trade-off between imaging speed and spatial resolution. The proposed method was validated on resolution test targets and bovine cancellous bone samples to demonstrate the capability of PADA U-Net in recovering full-scanning images from under-sampled OR-PAM images. With a down-sampling ratio of [4, 1], compared to bilinear interpolation, the Peak Signal-to-Noise Ratio and Structural Similarity Index Measure values (averaged over the test set of bovine cancellous bone) of the PADA U-Net were improved by 2.325 dB and 0.117, respectively. The results demonstrate that the PADA U-Net model reconstructed the OR-PAM images well with different levels of sparsity. Our proposed method can further facilitate early diagnosis and treatment of bone diseases using OR-PAM. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the stress distribution in cortical and cancellous bones and within the screw when a stainless steel extra-alveolar screw (EA-S) is inserted into the retromolar region of the mandible using the finite element method (FEM). The stress values in the EA-S were highest at 60° with horizontal (shear) force and lowest at 90° with axial force. In the bones (cortical and cancellous), the stress value was greatest at 90° with horizontal force. Greater stability of the screw may be achieved by tilting it to the force when horizontal loads are applied. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to present optimized device‐specific low‐dose cone‐beam computed tomography (CBCT) protocols with sufficient image quality for pre‐surgical diagnostics and three‐dimensional (3D) modelling of cleft defects. Methods: Six paediatric skulls were acquired, and an artificial bony cleft was created. A high‐resolution CBCT scan acted as a reference standard (Accuitomo 170, Morita, Kyoto, Japan) for comparing eight low‐dose protocols of Newtom VGi‐evo (QR Verona, Cefla, Verona, Italy), which included Eco and Regular protocols with different field of views (FOVs). Delineation of lamina dura, cementoenamel junction (CEJ), trabecular bone and bony bridge were assessed. A 3D model of the defect was also evaluated. Result: The dose area product of low‐dose protocols ranged from 31 to 254 mGy*cm2. Despite the dose difference of up to eight times between applied protocols, trabecular bone and CEJ exhibited appropriate image quality in all scans. However, Regular small FOV protocols (5 × 5 and 8 × 5 cm2), for both lamina dura and bony bridge, demonstrated a significant improvement in image quality compared to Eco FOV counterparts. Based on 3D defect analysis, no significant difference existed between low‐dose protocols and the reference standard. Conclusion: The findings highlight the possibility of achieving a considerable reduction (up to eight times) in the radiation dose using low‐dose CBCT protocols while maintaining sufficient image quality for assessing anatomical structures and 3D modelling in cleft cases. [ABSTRACT FROM AUTHOR]

Bone fractures often require internal fixation using plates or screws. Normally, these devices are made of permanent metals like titanium providing necessary strength and biocompatibility. However, they can also cause long-term complications and may require removal. An interesting alternative are biocompatible degradable devices, which provide sufficient initial strength and then degrade gradually. Among other materials, biodegradable magnesium alloys have been developed for craniofacial and orthopaedic applications. Previously, we tested implants made of magnesium hydroxide and RS66, a strong and ductile ZK60-based alloy, with respect to biocompatibility and degradation behaviour. Here, we compare the effects of dissolving magnesium hydroxide and RS66 cylinders on bone regeneration and bone growth in rabbit condyles using microtomographical and histological analysis. Both magnesium hydroxide and RS66 induced a considerable osteoblastic activity leading to distinct but different spatio-temporal patterns of cancellous and periosteal bone growth. Dissolving RS66 implants induced a prominent periosteal bone formation on the medial surface of the original condyle whereas dissolving magnesium hydroxide implants enhance mainly cancellous bone formation. Especially periosteal bone formation was completed after 6 and 8 weeks, respectively. The observed bone promoting functions are in line with previous reports of magnesium stimulating cancellous and periosteal bone growth and possible underlying signalling mechanisms are discussed. Biodegradable magnesium based implants are promising candidates for use in orthopedic and traumatic surgery. Although these implants are in the scientific focus for a long time, comparatively little is known about the interactions between degrading magnesium and the biological environment. In this work, we investigated the effects of two degrading cylindrical magnesium implants (MgOH 2 and RS66) both on bone regeneration and on bone growth. Both MgOH 2 and RS66 induce remarkable osteoblastic activities, however with different spatio-temporal patterns regarding cancellous and periosteal bone growth. We hypothesize that degradation products do not diffuse directionless away, but are transported by the restored blood flow in specific spatial patterns which is also dependent on the used surgical technique. [Display omitted] [ABSTRACT FROM AUTHOR]

Large-volume autologous iliac cancellous bone grafting for alveolar cleft may lead to undesirable bone resorption and susceptible donor-site morbidity, whereas the addition of deproteinized bovine bone (DBB) could optimize outcomes. This study aimed to evaluate the effectiveness of combining autologous iliac bone with DBB using three-dimensional cone beam computed tomography (3D-CBCT) for better analysis of bone generation than conventional evaluation methods. Thirty-six patients with unilateral alveolar cleft were assigned into two groups. Group A (n = 21) underwent autogenous cancellous bone graft harvested from the anterior iliac crests, while Group B (n = 15) received a composite of autogenous iliac cancellous bone and DBB. Patients in Group B displayed higher bone filling rates (P < 0.0001) and lower bone absorption rates (P < 0.001) than those in Group A at both 6 months and 1 year postoperatively. Additionally, there were directional differences in bone absorption within the bone grafts, with more absorption observed on the alveolar crest and palatal sides than that on the nasal and labial sides (P < 0.001). This study demonstrates that employing a combination of DBB and autologous bone in alveolar cleft repair achieves better outcomes of bone grafting. [ABSTRACT FROM AUTHOR]

Higher stature and lower weight are associated with increased risk of fracture. However, the pathophysiology for the associations of height and weight with bone microarchitecture and geometry is unclear. We examined whether these associations were consistent with causation and/or with shared familial factors. In this cross-sectional study of 566 female twins aged 26-76 yr, a regression analysis for twin data, Inference about Causation by Examination of FAmilial CONfounding (ICE FALCON), was used for testing causation. The bone microarchitecture and geometry of the distal tibia was assessed using HR-pQCT and the StrAx1.0 software. Higher stature was associated with larger total bone cross-sectional area (CSA), lower total bone volumetric bone mineral density (vBMD), larger cortical CSA, thinner cortices, higher porosity of the total cortex, compact cortex, outer and inner transitional zone (TZ), lower cortical vBMD, and larger medullary CSA (regression coefficients (β) ranging from −.37 to.60, all p<.05). Using ICE FALCON, the cross-pair cross-trait associations attenuated toward zero after adjusting for the within-individual association (absolute values of β ranging from.05 to.31, all p<.001). Higher weight was associated with higher total bone vBMD, larger cortical CSA and thicker cortices, lower porosity of the total cortex and inner TZ, and higher cortical vBMD (β ranging from −.23 to.34, all p<.001), and thinner trabeculae, higher trabecular number, lower trabecular separation, and higher trabecular vBMD (β ranging from −.31 to.39, all p<.05). Only cortical CSA attenuated toward zero after adjusting for the within-individual association between weight and bone microarchitecture (β = .042, p=.046). Higher stature was associated with a weaker cortical, not trabecular bone traits, whereas higher weight was associated with stronger cortical and trabecular bone traits. The results were consistent with height having a causal effect on weaker cortical bone structure, whereas weight had a casual effect on the larger cortical CSA. Lay Summary: Height and weight are associated with the bone structure and the likelihood of suffering a fragility fracture. Taller women have an increased risk of hip, wrist, and spine fracture, while heavier women have a lower risk of hip fracture and a higher risk of fractures in the ankle, leg, or upper arm. To give patients better advice regarding bone health, we need to know more about how height and weight are related to the bone structure. We examined measurements from high-resolution radiological investigation of the distal tibia obtained from 566 female Australian twins aged 26-76 yr. We used a statistical method (ICE-FALCON) that can detect whether the results are likely to be causal by using cross sectional twin data. The analysis showed that taller women had a weaker architecture in the outer part of their wider bone, while heavier women had a stronger architecture in both the outer and inner porous part of the bone. The ICE-FALCON analysis showed that the height itself is likely to have a causal relationship with most of the bone structure of the distal tibia, while weight was unlikely to have a causal relationship with most of the bone traits measures. Graphical Abstract [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a prevalent disease and has been associated with an increased fracture risk despite normal or even higher areal BMD. The aim of this study was to estimate the association between glucose metabolism status (GMS) and measurements of glycemic control with HRpQCT parameters of bone microarchitecture and strength. Participants of the Maastricht study who underwent an HRpQCT scan at the distal radius and tibia were included. GMS was determined by use of an oral glucose tolerance test and grouped into a normal glucose metabolism (NGM), prediabetes, or T2D. Linear regression models were used, stratified by sex with multiple adjustments. This study incorporated cross-sectional data from 1400 (796 [56.9%] NGM, 228 [16.3%] prediabetes, and 376 [26.9%] T2D) men and 1415 (1014 [71.7%] NGM, 211 [14.9%] prediabetes, and 190 [13.4%] T2D) women. The mean age was 59.8 ± 8.6 and 57.6 ± 9.0 yr for men and women, respectively. After adjustment, T2D was associated with a higher total BMD measured by HRpQCT and cortical thickness, and a smaller total and trabecular area in men and women compared with NGM. In women, T2D was additionally associated with a higher stiffness and failure load at the radius. Results were more pronounced at the distal radius than at the distal tibia. To conclude, these findings suggest that in this cohort of Maastricht study participants, total and trabecular bone area are smaller, but bone microarchitecture, density, and bone strength assessed by HRpQCT are not impaired in individuals with T2D. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study Objectives: The criteria for determining completion of intervertebral stability after posterior lumbar interbody fusion (PLIF) remain controversial. Several new radiological indicators of bone growth and osteointegration have been established. We compared computed tomography (CT) findings related to osteointegration after PLIF with interbody cages of two different materials and designs. Methods: We retrospectively analyzed data from 103 patients who underwent PLIF with three-dimensional porous tantalum (Tn) cages or titanium-coated polyetheretherketone (TiP) cages. CT images obtained 3 months and 1 year after surgery were examined for trabecular bone remodeling (TBR), cancellous condensation (CC), and vertebral endplate cyst (VEC) formation. The incidences of each finding were compared by cage type, and rates of instrument failure and pseudarthrosis were determined. Results: Three months postoperatively, 87% of the levels with Tn cages exhibited TBR, whereas 96% of those with TiP cages did not (P <.001). Most levels with Tn cages levels exhibited TBR and no CC 3 months (81%) and 1 year (94%) after surgery. Although 78% of levels with TiP cages exhibited CC and no TBR 3 months after surgery, 59% exhibited both CC and TBR 1 year after surgery. Significantly fewer VECs formed around the Tn cages than around the TiP cages both 3 months (P =.002) and 1 year (P <.001) after surgery. Implant-related problems occurred at levels that exhibited neither TBR nor CC. Conclusions: The porous tantalum cage may enable intervertebral stability that is comparable to bony fusion soon after surgery. [ABSTRACT FROM AUTHOR]

It is unknown whether activity-based physical therapy (ABPT) modalities that mobilize the paralyzed limbs improve bone integrity at the highly fracture-prone epiphyseal regions of the distal femur and proximal tibia following severe spinal cord injury (SCI). In this study, 4-mo-old skeletally mature littermate-matched male Sprague-Dawley rats received either SHAM surgery or severe contusion SCI. At 1 wk postsurgery, SCI rats were stratified to undergo no-ABPT, two 20-min bouts/day of quadrupedal bodyweight-supported treadmill training (qBWSTT), or hindlimb passive isokinetic bicycle (cycle) training, 5 days/wk for another 3 wk. We assessed locomotor recovery and plantar flexor muscle mass, tracked cancellous and cortical bone microstructure at the distal femoral and proximal tibial epiphyses using in vivo microcomputed tomography (microCT), and evaluated bone turnover at the tibial epiphysis with histomorphometry. All SCI animals displayed persistent hindlimb paralysis and pervasive muscle atrophy. Over the initial 2 wk, which included 1 wk of no exercise and 1 wk of ABPT acclimation, a similar magnitude of bone loss developed in all SCI groups. Thereafter, cancellous bone loss and cortical bone decrements increased in the SCI no-ABPT group. qBWSTT attenuated this trabecular bone loss but did not prevent the ongoing cortical bone deficits. In comparison, twice-daily cycle training increased the number and activity of osteoblasts versus other SCI groups and restored all bone microstructural parameters to SHAM levels at both epiphyseal sites. These data indicate that a novel passive isokinetic cycle training regimen reversed cancellous and cortical bone deterioration at key epiphyseal sites after experimental SCI via osteoblast-mediated bone anabolic mechanisms, independent of locomotor recovery or increased muscle mass. NEW & NOTEWORTHY: This study was the first to assess how quadrupedal bodyweight-supported treadmill training or passive isokinetic bicycle (cycle) training impacts bone recovery at the distal femoral and proximal tibial epiphyses in a rat model of severe contusion spinal cord injury. Our results demonstrate that passive isokinetic cycle training completely restored cancellous and cortical bone microstructural parameters at these sites via osteoblast-mediated bone anabolic actions, independent of locomotor recovery or increased plantar flexor muscle mass. [ABSTRACT FROM AUTHOR]

Objectives We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis. Methods Patients diagnosed with axial spondyloarthritis were included in this cross-sectional study. Dual-energy X-ray absorptiometry was used to measure BMD in the lumbar spine and TBS. Low TBS was defined as ≤1.31. The association between TBS and disease parameters including Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, BASFI and BASMI was studied using logistic regressions. Results Our study included 56 patients, with a mean age of 38.9 ± 13.5 years and a mean disease duration of 12.7 ± 7.7 years. Patients with low TBS were significantly older and had higher waist circumference and body mass index. These patients also showed greater clinical activity, as evidenced by higher ASDAS-CRP, BASFI and BASMI scores (P  < 0.05). In multivariate logistic regression, low TBS was associated with all disease parameters, except for BASMI: BASDAI (OR [95% CI] = 3.68 [1.48–9.19], P  = 0.005), ASDAS-CRP (OR [95% CI] = 2.92 [1.20–7.10], P  = 0.018), BASFI (OR [95% CI] = 1.04 [1.01–1.08], P  = 0.018), BASMI (OR [95% CI] = 1.36 [0.99–1.87], P  = 0.062). However, no association was observed between TBS and VFs. Conclusion TBS was associated with active spondyloarthritis, suggesting increased bone fragility in these patients. However, TBS failed to demonstrate an association with VFs. [ABSTRACT FROM AUTHOR]

With the aid of 3D printing, this study attempts to calculate the effective elastic modulus as well as the dimensional correctness and porosity of bolt samples. The main contribution of this study is the identification of the bolt sample porosity that is most appropriate for use as cancellous bone implants. It was discovered by contrasting the printed bolt sample's size, porosity, and effective modulus of elasticity with cancellous bone, as well as with the CAD model. This study examines the characteristics of bolt PLA samples created using SolidWorks software and manufactured in three dimensions using FDM. Observing the uniaxial tensile and determining its elasticity using stress-strain curves were the goals. Three of the five bolt samples used in the tests yielded essentially accurate results. Our research will aid in comprehending numerous facets of creating, testing, and optimising 3-D printed PLA bolts for use in real-world applications. The effective modulus of elasticity is generated by computer simulation using the MSC Marc software. Bolts with porosity variations of 42.9 percent and 58.1 percent revealed that the results of the printed bolt were flawless, but those with porosity variations of 22.3 percent and 73.4 percent generated incorrect impressions because they had too few pores or features. However, bolts with porosities of 58.1 and 73.4 percent exhibited a suitable elastic modulus that matched the span of cancellous bone. The bolt with a porosity of 58.1 percent was found to be the most suitable for usage as a cancellous bone implant with precise fabrication results. [ABSTRACT FROM AUTHOR]

The article titled "HOW TO AVOID FAILURES IN CORTICO BASAL IMPLANTOLOGY: PART-1" by Dr. Muhammad Shafie discusses the importance of understanding and properly executing corticobasal implantology. The author emphasizes that while this technology offers faster and hassle-free restoration of lost teeth, it requires a good understanding and patience for successful results. The article provides guidance on topics such as basal bone, stabilization of implants, and implant design. It also suggests various methods for stabilizing implants at the abutment level. Overall, the article aims to help clinicians avoid failures in corticobasal implantology by providing essential knowledge and sequencing for successful outcomes. [Extracted from the article]

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